Myeloid leukemias have proven to be particularly unresponsive to glucocorticoid therapy, a regimen shown to be quite useful in the treatment of T and B cell leukemias. We have investigated the in vitro sensitivity of several myeloid tumor cell lines, including HL6O and U937, to various sex steroids, including estradiol, diethylstilbestrol (DES), progesterone and testosterone. All cell lines tested proved to be killed by amounts of estradiol, DES and progesterone ranging from l0-l00uM. DES proved the most effective. The method of cell death appears to involve cytoplasmic swelling and extrusion of nuclei, accompanied by DNA degradation. Leukemias sensitive to hydrocortisone and dexamethasone, such as T and B cell leukemias, were also quite sensitive to DES, estradiol and progesterone. All cell lines tested were found to possess receptors for estradiol (which are shared by DES), but no receptors for progesterone could be detected. In vivo studies of drug effectiveness against myeloid tumor xenograft growth in athymic mice are underway.